We recently measured this hormone in the stored EPS urine specimens, and developed an algorithm for identifying the LH surge as a marker of ovulation. Both the LH surge and the DLT were found to be highly accurate in estimating day of ovulation. We hypothesized and found that low progesterone as measured by low midluteal levels and a slower rate of increase after ovulation, was related to reduced fecundability, suggesting that the normal variability in luteal progesterone among women in the general population is also a determinant of fecundability, not just the clinically defined condition. High LH was associated with increased fecundability. Thus, in women with no known fertility problems, there is little evidence of a subclinical polycystic ovary-type syndrome. On the other hand, there is evidence that normal variability in the pituitary hormone levels is associated with fecundability and that higher levels are advantageous. We described patterns of corpus luteum rescue. The early pregnancy study data show an abrupt rise in progesterone for the majority of clinical pregnancies (those surviving at least six weeks after last menstrual period). However, the timing of the abrupt rise does not always follow immediately after implantation (when human CG (hCG) first reaches the maternal circulation). About one out of six clinical pregnancies showed no progesterone rise at all during the first week after implantation, despite the exponentially increasing concentrations of hCG in these pregnancies. Thus, the abrupt progesterone rise does not appear to be determined exclusively by hCG. Maintenance of midluteal progesterone levels is apparently sufficient to inhibit uterine contractions, so another function such as immune suppression, may be provided by the abrupt rise in progesterone. We are currently examining corpus luteum rescue in occult pregnancies (those that are lost within six weeks of the last menstrual period) to see whether failure of the corpus luteum can account for any of the early loss. Other Fertility Research Clarice Weinberg initiated a study of infertile couples undergoing an in vitro fertilization (IVF) cycle, and I collaborated on the study. Egg maturation, semen quality, fertilization, and implantation/early conceptus survival are examined separately for whether smoking or caffeine affected any of these processes. One hundred seventy couples who were treated through the IVF clinic at the University of North Carolina participated in the study. Both male and female partners completed a self-administered questionnaire during the IVF treatment cycle. They provided information about smoking, caffeine, and other exposures. Neither current smoking nor caffeine were associated with reduced egg counts or lower fertilization or cleavage rates. Thus, if these exposures have adverse effects on follicle development, egg maturation, or semen quality, they appear to be overcome by the hormonal treatments used during the IVF cycle. We collected data in the Agricultural Health Study (see Sandler, Rowland sections) to examine factors related to variation in menstrual cycle characteristics. In preparation for analysis of possible associations with pesticide exposure, we examined common exposures such as cigarette smoking and variation in body mass. There was a strong dose-response association between increased body mass and risk of having long or irregular menstrual cycles (both of which were related to infertility in the study women). This suggests that the growing levels of obesity in this country and elsewhere, will have adverse reproductive effects.